Running exercise mitigates the negative consequences of chronic stress on dorsal hippocampal long-term potentiation in male mice.

In the hippocampus, learning and memory are likely mediated by synaptic plasticity, known as long-term potentiation (LTP). While chronic intermittent stress is negatively correlated, and exercise positively correlated to LTP induction, we examined whether exercise could mitigate the negative consequences of stress on LTP when co-occurring with stress. Mice were divided into four groups: sedentary no stress, exercise no stress, exercise with stress, and sedentary with stress. Field electrophysiology performed on brain slices confirmed that stress alone significantly reduced dorsal CA1 hippocampal LTP and exercise alone increased LTP compared to controls. Exercise with stress mice exhibited LTP that was significantly greater than mice undergoing stress alone but were not different from sedentary no stress mice. An ELISA illustrated increased corticosterone in stressed mice compared to no stress mice. In addition, a radial arm maze was used to examine behavioral changes in memory during 6 weeks of stress and/or exercise. Exercised mice groups made fewer errors in week 2. RT-qPCR was used to examine the mRNA expression of components in the stress and exercise pathways in the four groups. Significant changes in the expression of the following targets were detected: BDNF, TrkB, glucocorticoid, mineralocorticoid, and dopamine 5 receptors. Collectively, exercise can mitigate some of the negative impact stress has on hippocampal function when both occur concurrently.

Advances in Proton Therapy for the Management of Head and Neck Tumors.

Proton therapy (PBRT) is a form of external beam radiotherapy with several dosimetric advantages compared with conventional photon (x-ray) radiotherapy. Unlike x-rays, protons deposit most of their dose over a finite range, with no exit dose, in a pattern known as the Bragg peak. Clinically, this can be exploited to optimize dose to tumors while delivering a lower integral dose to normal tissues. However, the optimal role of PBRT is not as well-defined as advanced x-ray-based techniques such as intensity-modulated radiotherapy.

A 65-Year-Old Man with Recent History of Radiation Therapy to the Head and Neck Reporting for Treatment of a Non-restorable Tooth.

Patients with a history of head and neck radiation involving or adjacent to tooth-bearing areas are at increased risk of developing osteonecrosis following dental procedures. The dental provider should thus aim to preserve the patient's dentition after radiation therapy. Root canal therapy with coronectomy may be an option for a nonrestorable tooth, whereas atraumatic extraction can be considered if retaining the tooth is impossible. When treating a patient with a history of head and neck radiation, it is recommended that the dental provider reviews the patient's radiation records and consults with the patient's radiation oncologist to better stratify treatment risks.

Positron Emission Tomography (PET)/Computed Tomography (CT) Imaging in Radiation Therapy Treatment Planning: A Review of PET Imaging Tracers and Methods to Incorporate PET/CT.

Purpose: Positron emission tomography (PET)/computed tomography (CT) has become a critical tool in clinical oncology with an expanding role in guiding radiation treatment planning. As its application and availability grows, it is increasingly important for practicing radiation oncologists to have a comprehensive understanding of how molecular imaging can be incorporated into radiation planning and recognize its potential limitations and pitfalls. The purpose of this article is to review the major approved positron-emitting radiopharmaceuticals clinically being used today along with the methods used for their integration into radiation therapy including methods of image registration, target delineation, and emerging PET-guided protocols such as biologically-guided radiation therapy and PET-adaptive therapy. Methods and Materials: A review approach was utilized using collective information from a broad review of the existing scientific literature sourced from PubMed search with relevant keywords and input from a multidisciplinary team of experts in medical physics, radiation treatment planning, nuclear medicine, and radiation therapy. Results: A number of radiotracers imaging various targets and metabolic pathways of cancer are now commercially available. PET/CT data can be incorporated into radiation treatment planning through cognitive fusion, rigid registration, deformable registration, or PET/CT simulation techniques. PET imaging provides a number of benefits to radiation planning including improved identification and delineation of the radiation targets from normal tissue, potential automation of target delineation, reduction of intra- and inter-observer variability, and identification of tumor subvolumes at high risk for treatment failure which may benefit from dose intensification or adaptive protocols. However, PET/CT imaging has a number of technical and biologic limitations that must be understood when guiding radiation treatment. Conclusion: For PET guided radiation planning to be successful, collaboration between radiation oncologists, nuclear medicine physicians, and medical physics is essential, as well as the development and adherence to strict PET-radiation planning protocols. When performed properly, PET-based radiation planning can reduce treatment volumes, reduce treatment variability, improve patient and target selection, and potentially enhance the therapeutic ratio accessing precision medicine in radiation therapy.

Virtual reality-based simulation improves gynecologic brachytherapy proficiency, engagement, and trainee self-confidence.

PURPOSE: Intracavitary brachytherapy is critical in treatment of cervical cancer with the highest rates of local control and survival. Only about 50% of graduating residents express confidence to develop a brachytherapy practice with caseload as the greatest barrier. We hypothesize that virtual reality (VR)-based intracavitary brachytherapy simulation will improve resident confidence, engagement, and proficiency. METHODS: We created a VR training video of an intracavitary brachytherapy case performed by a board-certified gynecologic radiation oncologist and medical physicist. Residents performed a timed intracavitary procedure on a pelvic simulator before and after viewing the VR simulation module on a commercially available VR headset while five objective measures of implant quality were recorded. The residents completed a pre- and postsimulation questionnaire assessing self-confidence, procedural knowledge, and perceived usefulness of the session. RESULTS: There were 14 residents, including five postgraduate year (PGY)-2, three PGY-3, four PGY-4, and two PGY-5, who participated in the VR curriculum. There were improvements in resident confidence (1.43-3.36), and subjective technical skill in assembly (1.57-3.50) and insertion (1.64-3.21) after the simulation. Average time of implant decreased from 5:51 to 3:34 (p = 0.0016). Median technical proficiencies increased from 4/5 to 5/5. Overall, the residents found VR to be a useful learning tool and indicated increased willingness to perform the procedure again. CONCLUSIONS: VR intracavitary brachytherapy simulation improves residents' self-confidence, subjective and objective technical skills, and willingness to perform brachytherapy. Furthermore, VR is an immersive, engaging, time-efficient, inexpensive, and enjoyable tool that promotes residents interest in brachytherapy.

Multi-Institutional Analysis of Synchronous Prostate and Rectosigmoid Cancers.

Purpose: To perform a multi-institutional analysis of patients with synchronous prostate and rectosigmoid cancers. Materials and Methods: A retrospective review of Duke University and Durham Veterans Affairs Medical Center records was performed for men with both prostate and rectosigmoid adenocarcinomas from 1988 to 2017. Synchronous presentation was defined as symptoms, diagnosis, or treatment of both cancers within 12 months of each other. The primary study endpoint was overall survival. Univariate and multivariable Cox regression was performed. Results: Among 31,883 men with prostate cancer, 330 (1%) also had rectosigmoid cancer and 54 (16%) of these were synchronous. Prostate cancer was more commonly the initial diagnosis (59%). Fifteen (28%) underwent prostatectomy or radiotherapy before an established diagnosis of rectosigmoid cancer. Stage I, II-III, or IV rectosigmoid cancer was present in 26, 57, and 17% of men, respectively. At a median follow-up of 43 months, there were 18 deaths due rectosigmoid cancer and two deaths due to prostate cancer. Crude late grade ≥3 toxicities include nine (17%) gastrointestinal and six (11%) genitourinary. Two anastomotic leaks following low anterior resection occurred in men who received a neoadjuvant radiotherapy prostate dose of 70.6-76.4 Gy. Rectosigmoid cancer stages II-III (HR 4.3, p = 0.02) and IV (HR 16, p < 0.01) as well as stage IV prostate cancer (HR 31, p < 0.01) were associated with overall survival on multivariable analysis. Conclusions: Synchronous rectosigmoid cancer is a greater contributor to mortality than prostate cancer. Men aged ≥45 with localized prostate cancer should undergo colorectal cancer screening prior to treatment to evaluate for synchronous rectosigmoid cancer.

Stereotactic body radiation therapy versus sublobar resection for stage I NSCLC.

PURPOSE: To compare sublobar resection and stereotactic body radiation therapy (SBRT) in patients with stage I non-small cell lung cancer (NSCLC). METHODS: Patients undergoing sublobar resection or SBRT for stage I NSCLC from 2007 to 2014 at Duke University Medical Center were evaluated. The primary endpoint of interest was freedom from local recurrence. Kaplan-Meier survival estimates and Cox proportional hazards multivariate analyses were performed. RESULTS: 221 patients with stage I NSCLC undergoing sublobar resection (n = 151; 105 wedge and 46 segmentectomy) or SBRT (n = 70) were evaluated. The majority (89%) of patients receiving SBRT were medically inoperable, and compared with surgical patients, were significantly older (74 vs 70 years, p = 0.019), had higher Charlson Comorbidity Indices (3.7 vs 2.7, p < 0.001), larger tumors (2.4 cm vs 1.7 cm, p < 0.001), and worse baseline pulmonary function. At 3 years, freedom from local recurrence was 90% (95% CI 82-94%) for surgery and 85% (95% CI 65-94%) for SBRT (p = 0.71). While overall survival and disease-free survival were higher in the surgical cohort, no differences were noted in cancer-specific disease-free survival (60% vs. 65%, p = 0.84). On multivariate analysis, higher Charlson Comorbidity Index (HR 1.38, 95% CI 1.19-1.61, p < 0.001) and lower diffusion capacity (HR 0.97, 95% CI 0.96-0.98, p < 0.001) were independently associated with inferior overall survival. No differences in overall survival between surgery and SBRT (HR 1.20, 95% CI 0.74-1.95, p = 0.46) were observed after correcting for baseline imbalances in prognostic factors. CONCLUSIONS: SBRT and sublobar resection provided similar rates of local tumor control and overall clinical outcomes in stage I NSCLC.